Fosfomycin susceptibility of Escherichia coli urinary tract infection isolates from Australia

Background: The elderly population has elevated rates of UTIs compared to younger demographics. These individuals are at increased risk of acquiring drug-resistant bacterial infections due to multiple factors. Following the increasing prevalence of extended-spectrum β-lactamases and carbapenem-resistant Enterobacterales, fosfomycin, a broad-spectrum antibiotic, has been approved for the treatment of uncomplicated urinary tract infections (UTIs) caused by Escherichia coli in many countries. In Australia fosfomycin tromethamine was approved by the Therapeutic Goods Administration in 2017 for the treatment of uncomplicated UTIs in females >12 years of age. Aims: In 2019 and 2020 we performed a cross-sectional study to identify and characterise fosfomycin-resistant UTI-causing E. coli isolates in Australia. Methods: A total of 2,056 non-duplicate UTI E. coli isolates were collected from six Australian institutions and screened for fosfomycin resistance. Using whole genome sequencing (WGS) polymorphisms and genes associated with fosfomycin resistance were investigated. Results: Overall 99.8% of isolates were fosfomycin susceptible. Only five non-related fosfomycin resistant isolates were identified. Two isolates harboured an identical plasmid-encoded fosA4 fosfomycin resistance gene. Fosfomycin resistance in the remaining three isolates was chromosomally encoded and attributed to single nucleotide polymorphisms. Conclusions: Fosfomycin resistance in UTI E. coli isolates in Australia is rare. However to minimise the emergence and spread of resistance via horizontal gene transfer, it is recommended fosfomycin be reserved for the treatment of acute uncomplicated UTI patients when the standard first-line drugs are not an option.